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AMPA Receptor Activation Causes Silencing of AMPA Receptor-Mediated Synaptic Transmission in the Developing Hippocampus Pontus Wasling*, Joakim Strandberg, Eric Hanse Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Abstract Agonist-induced internalization of transmembrane receptors is a widespread biological phenomenon that also may serve as a mechanism for synaptic plasticity. Here we show that the agonist AMPA causes a depression of AMPA receptor (AMPAR) signaling at glutamate synapses in the CA1 region of the hippocampus in slices from developing, but not from mature, rats. This developmentally restricted agonist-induced synaptic depression is expressed as a total loss of AMPAR signaling, without affecting NMDA receptor (NMDAR) signaling, in a large proportion of the developing synapses, thus creating AMPAR silent synapses. The AMPA-induced AMPAR silencing is induced independently of activation of mGluRs and NMDARs, and it mimics and occludes stimulus-induced depression, suggesting that this latter form of synaptic plasticity is expressed as agonist-induced removal of AMPARs. Induction of long-term potentiation (LTP) rendered the developing synapses resistant to the AMPA-induced depression, indicating that LTP contributes to the maturation-related increased stability of these synapses. Our study shows that agonist binding to AMPARs is a sufficient triggering stimulus for the creation of AMPAR silent synapses at developing glutamate synapses. Citation: Wasling P, Strandberg J, Hanse E (2012) AMPA Receptor Activation Causes Silencing of AMPA Receptor-Mediated Synaptic Transmission in the Developing Hippocampus. PLoS ONE 7(4): e34474. doi:10.1371/journal.pone.003447